Racemic endo-5-norbornen-2-ol can be obtained by heating dicyclopentadiene with vinyl acetate. The reaction requires a high temperature (typically &gt;160.degree. C.) at which the dicyclopentadiene is in equilibrium with the monomer cyclopentadiene that then undergoes Diels-Alder cycloaddition with the vinyl acetate. Pre-cracked cyclopentadiene cannot be used, as it dimerises faster than it reacts with the vinyl acetate. A consequence of the use of vinyl acetate is that, at the temperature of the reaction, it generates a significant pressure and specialised reactors are needed to contain this. The use of such specialised equipment adds markedly to the process cost.
The enantiomers of the 5-norbornen-2-ol which are of value as intermediates for pharmaceutical agents can be obtained by biocatalytic resolution, typically by treatment of an ester such as the acetate in a water-containing system with a lipase where one enantiomer is hydrolysed preferentially; see Eichberger et al, Tetrahedron Lett. (1986) 27:2843; and Oberhauser et al, Tetrahedron (1987) 43:3931. Alternatively, they can be obtained by biocatalyst-mediated esterification of the racemic alcohol with an acyl donor such as vinyl acetate in an organic solvent.
An issue following such a biotransformation is separation of the products. When these are the norbornenol and its acetate, the separation is difficult owing to the similarity of their physical properties; their boiling points are too similar for separation by distillation. While chromatographic separation is effective, that is not amenable to large-scale operation.